title: Stability of parenteral nanoemulsions loaded with paclitaxel: the influence of lipid phase composition, drug concentration and storage temperature.
abstract: Paclitaxel was loaded into licensed parenteral nutrition nanoemulsions (Clinoleic® and Intralipid®) using bath sonication, and the stability of the formulations was investigated following storage for two weeks at room temperature or at 4 °C. In general, Clinoleic droplets were smaller than Intralipid droplets, being around 255 and 285 nm, respectively, for blank and freshly loaded emulsions. Regardless of storage temperature, the Clinoleic exhibited a very slight or no increase in droplet size upon storage, whilst the droplet size of the Intralipid emulsion increased significantly. The droplet size of both emulsions was minimally affected by paclitaxel concentration within the range of 0, 1, 3 and 6 mg/ml. The pH of both emulsions markedly decreased upon storage at room temperature, which was possibly attributed to the production of fatty acids resulting from phospholipid hydrolysis. However, at 4 °C, the pH of Clinoleic emulsion was unaffected by storage or paclitaxel concentration while the Intralipid emulsion demonstrated a trend for pH reduction. Both nanoemulsions had a negative zeta potential, with the Clinoleic formulations having the highest charge, possibly explaining the better size stability of this emulsion. Overall, this study has shown that paclitaxel was successfully loaded into clinically licensed parenteral emulsions and that Clinoleic showed greater stability than the Intralipid.
authors.affiliation: Institute of Nanotechnology and Bioengineering, School of Pharmacy and Biomedical Sciences, University of Central Lancashire , Preston , United Kingdom .
authors.forename: Alisha N
authors.initials: AN
authors.lastname: Kadam
authors.forename: Mohammad
authors.initials: M
authors.lastname: Najlah
authors.forename: Ka-Wai
authors.initials: KW
authors.lastname: Wan
authors.forename: Waqar
authors.initials: W
authors.lastname: Ahmed
authors.forename: St John
authors.initials: SJ
authors.lastname: Crean
authors.forename: David A
authors.initials: DA
authors.lastname: Phoenix
authors.forename: Kevin M G
authors.initials: KM
authors.lastname: Taylor
authors.forename: Abdelbary M A
authors.initials: AM
authors.lastname: Elhissi
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D004355:Drug Stability; D004356:Drug Storage; D004655:Emulsions / Q000737:chemistry; D005217:Fat Emulsions, Intravenous / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage*; D010743:Phospholipids / Q000737:chemistry*; D010938:Plant Oils / Q000737:chemistry*; D013024:Soybean Oil / Q000737:chemistry*; D013696:Temperature
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C568346:ClinOleic; D004655:Emulsions; D005217:Fat Emulsions, Intravenous; D010743:Phospholipids; D010938:Plant Oils; C545823:soybean oil, phospholipid emulsion; D013024:Soybean Oil; D017239:Paclitaxel